SUMMARY: CORE E- BIOMARKER CORE. The Biomarker Core supports the Harvard Aging Brain Study (HABS) Program Project Grant (PPG) by processing and banking blood (plasma, serum, whole blood, buffy coat, RNA, miRNA, DNA and cell lines) and cerebrospinal fluid (CSF) samples (Aim 1) collected by the Clinical Core (Core B) from individuals (ages 50 to 94). Assays will be conducted on these biofluids to generate data on amyloid-b (A), tau (T) and neurodegeneration (N) (Aim 2) and data on vascular injury and immune response factors (Aim 3) for analysis by the Projects. The newly established Biomarker Core for HABS includes over 1300 biofluid samples (blood and CSF) from 373 participants in Grant Cycles 1 and 2, and will bank additional longitudinal samples over the next cycle. Bloods have been processed into plasma, serum, whole blood, buffy coat, RNA, miRNA, DNA and cell lines, and CSFs are collected, processed and stored according to best practices to minimize pre-analytical variability. ATN data has been generated using ultra- sensitive single molecule array (Simoa) technology with assays for Ab42, NT1 tau and neurofilament-light (NfL) in all samples to date as well as modifying factor data for vascular injury and immune response using electrochemiluminescence ELISA. Samples have been distributed to collaborating scientists for additional assays. Rigorous consideration of sample quality and assay sensitivity, specificity and precision have provided confidence in the assays that will be used in the next cycle. The Biomarker Core is comprised of a seasoned group of translational laboratory investigators with extensive experience in molecular neurosciences and neuropathology, neurology, psychiatry, and biorepository management. The Biomarker Core will work with the Clinical Core to continue optimal collection and on-site processing procedures for blood and CSF, bank and distribute biofluids, and generate ATN and modifying factor data using the most sensitive and reliable methods available. In order to bridge plasma with CSF and better understand the potential of blood biomarkers of brain health, we will generate data in simultaneously collected plasma and CSF in HABS and affiliated samples. Based on preliminary data and Project interests, in the next Cycle, the Biomarker Core will measure Ab42, NT1 tau and NfL, vascular injury markers (especially VEGF-related molecules) and Th1 and Th2 inflammatory markers (e.g., IFN-g and IL-4 respectively) and other associated markers. It will also continue to identify, evaluate and implement novel technologies and biomarkers for HABS. Data generated will be quality-controlled and transferred to DataCentral in coordination with the Analytic Core for use in Projects 1-4.